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Matrix Metalloproteinase Inhibitors: Current Developments and Future Perspectives

Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, Rotterdam, The Netherlands

Correspondence: Ronald Hoekstra, M.D., Department of Medical Oncology, University Hospital Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Fax: 31-10-463-4627; e-mail: hoekstra{at}oncd.azr.nl

Malignant tumors are characterized by invasive growth and metastasis. To facilitate this invasive behavior, the enzymatic breakdown of the extracellular matrix (ECM) is a prerequisite. Many human tumors are characterized by locally increased concentrations of matrix metalloproteinases (MMPs), enzymes that are able to degrade this ECM. A vast number of matrix metalloproteinase inhibitors (MMPIs) have been developed in recent years and after extensive preclinical testing, the results of the first clinical studies with several of these compounds have recently been presented. In this review we will describe some of the basic concepts of the degradation of the ECM, with special emphasis on the role of MMPs in the progression of cancer. Furthermore we will review the results of preclinical and clinical studies with MMPIs and discuss their future perspective.

Key Words. Matrix metalloproteinases • Matrix metalloproteinase inhibitors • Cancer • Clinical studies

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